The long term goal of this application is to study the role of peptides in shaping the repertoire of T-cells selected in the thymus. Towards this end, the investigator will utilize a novel mouse strain that expresses a single self peptide (CLIP) bound to all of its class II molecules (H2-M deficient mice). Most interesting, preliminary studies have shown that these mice display a very heterogenous T-cell repertoire and are highly autoreactive. These mice will be utilized to determine the precursor frequency of autoreactive T-cells, to analyze effector function of CD4+ T-cells that mature in such an environment, and to test the tolerogenicity of cortical thymic epithelial cells. An understanding of these processes is critical for understanding the mechanisms involved in thymic selection.